Innate immune mechanisms underlying the persistence of Zika virus in the human testis – INNATESTIS

Persistent viral infections of the male genital tract have far-reaching implication for human health, including diseases spreading. The emerging arbovirus Zika (ZIKV)is sexually transmitted by cured men and we demonstrated it persistently infects the human testis. We postulate that persistent testis infection is enabled by a specific innate immune response designed to ensure homeostasis in this immune privileged organ. In this project, we will use our unique ex vivo model of human testis together with cutting-edge transcriptomic techniques to decipher the cellular and molecular bases of ZIKV persistence (WP1) and perform in-depth mechanistic studies of new host persistence factors (WP2). Last but not least, we will develop a predictive experimental model of the persistence of emerging viruses in the testis and test antiviral approaches (WP3). For this, we have assembled a highly qualified consortium including experts in virology, innate immunity, molecular immunology, testis physiology and single cell genomics.